Is the Thyroglobulin Measurement Under Thyroxine of Prognostic Value Before rhTSH-Aided Radioiodine Ablation in Differentiated Thyroid Carcinoma?

Introduction Total (or near-total) thyroidectomy followed by TSH-stimulated administration of large activities of 131-iodine (131I) is the treatment of choice for DTC [1-3]. The serum thyroglobulin (Tg) measurement during hypothyroidism, just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease [4-8]. Recently recombinant human TSH (rhTSH) showed to be safely employed instead of thyroxine (T4) withdrawal (offT4) to prepare patients for radioiodine ablation [9-10]. However, the Tg level are measured 48 hours after radioiodine administration when rhTSH is used as stimulation [11]. Consequently, due to the radioiodine-induced thyroid cells damage and Tg release, the Tg measurement would not have reliable predictive value in patients treated by rhTSH stimulation [12]. The present study was undertaken to evaluate if preablativeTg measurement under T4 treatment is of prognostic value and serves as surrogate marker of offT4-stimulated preablative Tg.

Patients and methods

Patients selection We retrospectively enrolled 28 consecutive patients affected by histologically proven DTC (23 papillary, 5 follicular) submitted to total thyroidectomy and central compartment lymph-node dissection. Thyroxine (T4) treatment was started immediately after surgery to suppress TSH levels. Six to nine weeks later Tg levels were measured both basally (onT4-Tg) and after rhTSH (rhTSH-Tg) stimulation as previously described [13]. Subsequently, T4 was stopped for 4 weeks and serum Tg measured (offT4-Tg) just before 3700 MBq of 131I-iodide administration. A post-treatment whole body scan (PT-WBS) with radioiodine uptake (RAIU) calculation was performed according to a previously described protocol [1]. All non physiologic iodine uptake areas out of the thyroid bed were considered as positive findings [14, 15]. Patients with positive PT-WBS underwent specific treatment and personalized follow-up. Patients with negative PT-WBS immediately restarted T4 suppressive treatment. Final restaging was performed in all patients 12 months after the last treatment by neck ultrasound, onT4-Tg assay and both offT4-diagnostic WBS (DgWBS) and Tg assay (4 weeks T4 withdrawal; required TSH>30 mUI/L). Clinical and pathological characteristics of selected patients were summarized in the Table 1.

Serum Tg assay and screening for interferences Serum Tg was assayed in duplicate by a specific high-sensitive IRMA assay (DYNOtest® Tg-plus, BRAHMS Diagnostica GmbH, Berlin, Germany) according to the producer' instructions. This method provided a sensitivity of 0.05 ng/mL and a functional sensitivity of 0.2 ng/mL [16, 17]. As previously published, preablative offT4 serum Tg values above 4.5 ng/mL and 3.2 ng/mL were considered as positive with respect to PT-WBS and 12 months restaging results, respectively [8]. Otherwise, offT4-Tg values higher than 0.2 ng/ml measured 12 months after thyroid ablation were considered positive for persisting/relapsing disease. [18, 19]. The presence of anti-thyroglobulin antibodies (AbTg) was screened by a specific radioimmunoassay (DYNOtest® anti-TGn, BRAHMS Diagnostica GmbH, Berlin, Germany) and by recovery test with a specific Tg-recovery buffer provided by the producer. Sera showing AbTg levels more than 60 U/mL and/or recover less than 80% or more than 120% were excluded from the study. Quality control was ensured by assaying two levels of control sera in each series, by re-assessing all sera showing a coefficient of variation exceeding 10% and by a bimonthly partecipation in the European inter-laboratory control OncocheckTM.

Statistics Quantitative data are expressed as mean ± SD. Differences between groups were assessed by two-tailed unpaired t-test. The relationship between variables was assessed by linear regression analysis. In order to allow statistical analysis the value of undetectable serum Tg expressed as < 0.2 ng/nL was arbitrarily changed in 0.10 ng/mL. Statistical significance was defined by a p-value < 0.05.